The National Institute of Child Health has a longitudinal clinical program for children with types III and IV OI. The “longitudinal” character of the program refers to the fact that children can be enrolled as early as the newborn period and then potentially stay in the program until 25 years of age. Participants in the program form a community of patients who receive cutting edge treatment from a variety of specialists with decades of OI experience. The research aspect of the program involves enrollment in any of three protocols with different levels of research commitment. Families should not be apprehensive about the term “research”. Families can select a clinical track that involves mostly observational studies of the children or a more intensive program. Many OI clinics offer a clinical program that actually contains much of the same testing and treatment done at the NIH, but without the coordinated data gathering and comparison that happens as part of the NIH research. Often families may have to pay to participate in university hospital treatment or research programs; all the care provided for OI children at the NIH is free to the participants. The emphasis of the program in the first two years of life is on physical rehabilitation and genetics.

Patients may be referred by their local doctor or may self-refer. All new patients come to the NIH Clinical Center for an initial medical evaluation. This screening process provides the families with valuable medical information and assistance and allows them to determine whether they are interested in joining the NIH program. The medical staff of the BEMB also uses the screening visit to determine the suitability of the child for the program.

After the screening visit, children can enroll in any (or all) of the three major protocols: natural history, pamidronate, and growth hormone. Central to all three protocols is a major commitment to rehabilitation and physical therapy. Each visit includes rehab and PT evaluations in order to develop a home exercise plan that will optimize strength and endurance. OT and a staff pedorthist are also available at the discretion of the medical staff. The physical rehabilitation program for OI at the NIH is the best in the country, with over two decades of experience at maximizing physical potential, including ambulation. If a child is co-enrolled in two or three protocols, X-rays and other evaluations will not be duplicated; one schedule will be followed to incorporate the treatment protocols.

The natural history protocol is focused on the secondary effects that occur with OI. For the skeletal system, it includes radiographs and bone density scans, as well as careful examination and measurements every 4 months. Other evaluations such as neurology, cardiology, pulmonology, audiology, and dental examinations are all incorporated as soon as the child is able to cooperate. When problems arise, we work closely with the families, primary care physicians, orthopedists, or other specialists in order to ensure that appropriate actions are taken. The visit schedule is every 4 months, since this is the age of greatest development and fastest bone turnover. Genetics is also a major focus of the Natural History program. We can use blood and skin specimens, or bone from surgery, from patients and their families to identify the gene change that causes their OI; genetic counseling accompanies the testing results. Processing of specimens is handled in our own CLIA-certified lab without charge to families. Skin or bone cells and blood DNA is banked and kept indefinately so patients can benefit as future OI-research becomes applicable to their cases.

The pamidronate protocol has completed a 2-year randomized controlled trial that proved the benefit of a 2-3 yr course of the drug to the bones of the spine (vertebral bodies) in OI. Currently, we are conducting a dose-comparison trial for patients over 2 years of age.

The reasons for not treating with pamidronate under the age of 2 include the following: pamidronate inhibits bone turnover during the time of most active remodeling; it does not alleviate the associated syndromic short stature; it does not change the natural history of OI, and the children still require rodding. Finally, further research is required to identify the benefits and risks of treatment of children under the age of 2.

The growth hormone protocol focuses on alleviating the growth deficiency of OI; it can be combined with the pamidronate protocol. The growth protocol has one clinical plan for children who are 2- 4 years of age and another for those who are over 4 years old. The reason for this is that after one year of age, OI infants usually fall off the growth curve and enter a plateau phase until the age of about 4 years, when their growth rate often improves naturally. From age 2-4 yrs, the program includes blood work and physical measurements to help understand the cause of the growth plateau. After age 4, children are treated with growth hormone for at least one year and can continue on the hormone afterwards for as long as they meet responsiveness criteria.